New research has uncovered how manipulating levels of a brain neurotransmitter might help common memory and learning difficulties in multiple sclerosis.

Johns Hopkins University researchers said the results from their experiments, while very preliminary, are an encouraging development in the study of MS since cognitive impairment affects about 50 percent of patients, often in the prime of their lives.

"The cognitive impairment has a devastating effect for which we have absolutely no treatments and there is truly an unmet need of addressing it in MS," said Dr. Adam Kaplin, assistant professor of psychiatry and behavioral sciences and neurology at Johns Hopkins University School of Medicine, who led the study.

In the study, published in the Dec. 4 issue of the Proceedings of the National Academy of Sciences, the researchers first followed five newly diagnosed multiple sclerosis patients at baseline and four on disease-modifying therapies at follow-up. Magnetic resonance imaging with spectroscopy was used to evaluate brain chemicals in the hippocampus and the results were compared to their performance on cognitive tests.

The researchers found a strong correlation between low levels of N-acetylaspartylglutamate — an abundant signaling neurotransmitter — in the right hippocampus and lower cognitive function in six of the eight tests, including measures of processing speed, nonverbal learning, memory, sustained attention and cognitive flexibility.

The researchers then studied three groups of 10 mice each —control, mice with multiple sclerosis plus a type of placebo, and mice with MS treated with an experimental compound used in the study to increase the NAAG levels. Their memory was tested using a maze and other methods.

By the fourth day of testing, both the healthy mice and those with MS who had been given the compound — 2-(phosphonomethyl)pentanedioic acid (2-PMPA)— went through the maze equally well.

"By day 4, this didn't just improve their learning and memory a little bit, it got their learning and memory back to the level it would be if they didn't have MS at all," Kaplin said. Dr. Kristen Rahn, instructor in the department of psychiatry and behavioral sciences at Hopkins, was lead author of the study.

Kaplin said he wanted to show that depression — which he also researches — and cognitive impairment resulted from chemical changes in the brain caused by the illness.

"This would not only help remove the stigma about depression and cognitive impairment, but ... we could better diagnose, prognosticate and treat these consequences of MS," Kaplin said.

Dr. Susan Rubin, a Chicago-area neurologist who sees MS patients with cognitive troubles, said the study was striking because there was as yet no medication to treat the vexing problem.

"I think the exciting thing is just the capability to select some of these biomarkers for cognitive dysfunction and then having a chemical target that could be developed into a medication," said Rubin, vice chair of education in the department of neurology at NorthShore University Health System.

Rubin cautioned that the study was done on a small number of humans and mice and would need to be replicated on a much larger scale. "I think it's an interesting start and uses some interesting markers we probably need to know a little bit more about," Rubin said.

Rubin noted that many of the symptoms experienced by MS patients can be interrelated, including memory loss. Thus, if patients are tired, they don't exercise, then become stiffer and have more spasms, bladder and bowel trouble, insomnia, fatigue and resultant memory problems.

But for memory problems unrelated to other MS symptoms, only the drug donepezil — typically used for Alzheimer's patients — has been tested in multiple sclerosis and found ineffective.

Kaplin said he is working on a more effective delivery of 2-PMPA into the brain as a future solution to memory loss in MS patients. But he said drug companies would likely not be interested in developing the drug until researchers could "provide a patentable way that it can be delivered and to demonstrate that there is a large therapeutic market for its use."